Dispensing device and method for forming material

ABSTRACT

A dispensing device and method for forming a least partially solid or gel-like material from a liquid. At least one liquid issuing from an outlet is subjected to an electric field causing the liquid to form at least one electrically charged jet which, after formation, forms a fiber (F) or breaks up into fiber fragments (FF) or particles (D). The thus formed at least partially solid or gel-like material may be directly deposited, by virtue of the energy in the electrical field, onto a surface area, for example an area of skin enabling, for example, formation of a dressing for a wound or burn which is of high specific area and extremely absorbent. A biologically active ingredient such as a pharmaceutical ingredient or biological matter such as DNA may be incorporated into the fibers (F), fragments (FF) or particles (D). Fibrils, particles or microcapsules incorporating a biologically active ingredient may be supplied for oral or nasal administration to an animal such as a human being.

[0001] This invention relates to methods and devices for formingmaterial. In one example, this invention relates to methods and devicesfor applying material to a surface, for example to an internal orexternal surface of an animal, for example for applying material to skinfor use, for example, in the care or treatment of wounds or burns.

[0002] Various forms of aerosol devices for allowing material to besprayed onto a surface such as the human skin are known, includingaerosol devices for spraying wound care products onto wounds or burns.One such product is Savlon Dry (trade mark) which has been marketed inthe UK by Zyma Healthcare and Ciba Geigy plc. Such products require theuse of a gas propellant and in recent years the choice of gaspropellants has become more limited because of the desire to avoidenvironmentally unfriendly compounds such as a chlorofluorocarbons orhydrocarbons. Also because small droplets and powder particles tend tobe carried away from the target by the gas flow created when thepropellant gas hits and is deflected by the target surface, such gaspropelled sprays are generally designed to spray relatively largedroplets or powder particles in order to achieve sufficient inertia todeposit the spray on its target surface. Such gas propelled products mayrun if sprayed too freely, especially where the spray produces largedroplets. In addition, the packaging costs for such devices are high.

[0003] GB-A-1569707 describes a dispensing device for producing a sprayor cloud of liquid droplets intended primarily for crop spraying. Theprocess described in GB-A-1569707 produces liquid droplets by applyingan electric field to a liquid emerging from an outlet in the vicinity ofthe surface so that the liquid becomes sufficiently charged that the netelectric charge in the liquid as the liquid emerges into free spacecounteracts the surface tension forces of the liquid and the repulsiveforces generated by the like electrical charges cause the liquid to becomminuted to produce a cone or jet which breaks into liquid droplets.The droplets produced by this device are charged close to their RayleighLimit and thus in use migrate quickly toward conductive surfaces oflower or zero potential. This technique of comminuting liquid isgenerally known as electrohydrodynamic comminution.

[0004] In one aspect, the present invention provides a method and/or adevice for forming solid, partially solid or gel-like matter such asfibres, fibrils or fibre fragments or segments, droplets or particles byan electrohydrodynamic process. The thus formed matter may incorporateor have a core of a different material which may be for example abiologically active ingredient or material. The formed matter may beapplied to a surface or area such as, for example, the surface of theskin or a wound or burn or to a cavity, for example a body cavity. Thebody cavity may be the respiratory system of an animal such as a humanbeing, where the electrohydrodynamic process produces matter that doesnot block the respiratory system.

[0005] Where the resulting matter or material is to be applied orsupplied to a cavity or concave surface, then desirably the matter is atleast partially electrically discharged before application or supply.

[0006] In another aspect, the present invention provides a method ordevice for forming a mat or web by electrohydrodynamically formingelectrically charged fibres and/or fibrils in the vicinity of a surfaceor substrate. The present invention also provides a mat or web formedusing an electrohydrodynamic process.

[0007] In an aspect, the present invention provides a method or devicefor applying material to a surface by supplying to anelectrohydrodynamic site located in the vicinity of the surface liquidwhich is electrohydrodynamically processed at the site in such a mannerso as to form matter comprising at least partially solid or gel-likefibres, fibre fragments or fibrils or particles which are charged andare electrostatically attracted to the said surface enabling a mat orweb of randomly distributed fibres and/or fibrils and/or particles to beformed on the surface. The location at which the matter is deposited onthe surface can be at least partially controlled by effecting relativemovement between the surface and the matter.

[0008] In another aspect, the present invention provides a method ofapplying material to an exposed surface of an animal, for example to theskin or to a wound or burn or area exposed by a surgical procedure,which comprises producing material comprising at least one ofelectrically charged fibres, fibre fragments or fibrils or droplets orparticles in the vicinity of the said surface area by anelectrohydrodynamic process, so that the material deposits on the saidarea.

[0009] In another aspect, the present invention provides a method offorming fibre fragments or fibrils by supplying liquid to anelectrohydrodynamic site and deliberately perturbing the cone or jetissuing from the comminution site to cause the resulting fibre to breakup into fragments. The break up of the fibre may be promoted by pulsingthe voltage used for the electrohydrodynamic process. The length of thefibrils may be controlled by adjusting the frequency of the pulses.

[0010] In another aspect, the present invention provides a method offorming at least partly solid droplets or particles by supplying liquidto an electrohydrodynamic comminution site.

[0011] In an example, the present invention provides a method ofdepositing fibres on a surface, for example to form a dressing for asurface area of an animal for example an area of skin, a wound or burnor for other therapeutic or cosmetic reasons, which comprises supplyingliquid comprising polylactic acid having a molecular weight in theregion of 144000, dissolved 10% by mass in acetone at approximately 10milliliters per hour to an electrohydrodynamic comminution site locatedat about 5 to 10 cm above the surface.

[0012] In another example, the present invention provides a method ofdepositing fibres on a surface, for example to form a dressing for asurface area of an animal for example an area of skin, a wound or burnor for other therapeutic or cosmetic reasons, which comprises subjectingliquid comprising a biocompatible polymer which may be bioresorbable orbiodegradable polymer such as polylactic acid, polygylcolic acid,polyvinyl alcohol or polyhydroxybutyric acid to an electrohydrodynamicprocess in the vicinity of said area.

[0013] In an embodiment, the deposition process may be repeated one ormore times to provide a number of layers of material comprising at leastone of fibres, fibrils, droplets or particles on the surface. Thepolarity to which the material is charged may be reversed betweendeposition of different layers so as facilitate attraction between thelayers.

[0014] The liquid used to produce the electrohydrodynamically formedmatter may comprise a biologically active ingredient or component. Wherethe electrohydrodynamically formed material comprises fibrils, thefibrils may actually stick into the skin of soft tissue enablingdelivery of the active component to a location beneath the outer layerof skin or soft tissue.

[0015] The liquid used may comprise a solution, suspension,microsuspension, emulsion, microemulsion, gel or even a melt which maycontain an active component or components. Alternatively oradditionally, the active component may be provided as a coating or acore of the fibre, fibril or particle. For example microcapsules, fibresor fibrils of a bioresorbable or biodegradable polymer may be formedwhich contain a biologically active ingredient. Material from the coreof a fibre or fibril may be released from the ends of the fibre orfibril. Material from the core of a fibre, fibril or microcapsule may bereleased through the coating if the coating is permeable to the materialcontained within it or may be released as a result of the outer coatingbeing breached, for example by chemical or enzymic attack which causesthe outer coating to dissolve or degrade, by bioresorption orbiodegradation of the coating, or as a result of temperature changes orapplication of pressure which causes the outer coating to rupture. Thetiming of the release may be controlled, for a given polymer, bycontrolling the thickness of the coating surrounding the core.

[0016] Possible biologically active components for topical applicationare pharmaceutical compounds such as analgesics, antiseptics,antibiotics, antifungals, antibacterials, antiparasitics, debridementagents such as proteolytic enzymes, biological products such as cells,and cytokines for stimulating cytokinetic activity to promote essentialcell activities, for example, to stimulate dendritic growth, growthfactors such as fibroblast growth factor (FGF), epithelial growth factor(EGF), transforming growth factor (TGF) and others that may be used topromote or otherwise control the sequence of events essential to naturaltissue repair, DNA or other genetic material for gene therapy, cells,peptides or polypeptides, insulin, adjuvants, immune suppressants orstimulants, surface binding or surface recognising agents such assurface protein A, and surfactants. Where more than one layer of fibres,fibrils or droplets is deposited, then different active ingredients maybe provided in different layers.

[0017] Fibres, fibre fragments or particles of biological material suchas fibrin or collagen may be formed using a method embodying theinvention. Also electret polymers may be used to act as nuclei orotherwise initiate interactive cellular and/or molecular events intissue repair.

[0018] A number of electrohydrodynamic processing sites may be providedenabling different types of electrohydrodynamically formed matter to bedeposited at the same time.

[0019] The deposited material may be used alone or in combination with aconventional bandage or dressing. As another possibility, where thematerial contains, for example, a therapeutic agent, the material may bedeposited onto a conventional dressing to be applied to the skin.

[0020] In another aspect, the present invention provides a method ordevice for supplying comminuted material to the respiratory system of ananimal, which comprises electrohydrodynamically comminuting liquid so asto produce a plurality of at least partially solid or gel-like fibrilsor particles and supplying the fibrils or particles orally or nasally tothe animal. The comminuted material is preferably at least partiallyelectrically discharged before supply to the animal especially if it isto be delivered to the upper or lower reaches of the lungs rather thansimply to the nasal or oral passages.

[0021] The fibrils or particles may comprise biologically activematerial, for example the fibrils or particles may comprise DNAencapsulated in or complexed with a lipid for transfecting cells or may,for example, contain or encapsulate matter such as peptides,polypeptides and other large biomolecules such as insulin or growthfactor, and/or active pharmaceutical components for enabling delivery ofthe active component into the blood stream via the lung. This shouldprovide a quicker route to the bloodstream than that provided by normaloral ingestion and avoids the need for injection of components whichcannot be taken orally because of the gastric enzymes and acids presentin the digestive system. Microcapsules or fibrils for oral ingestion ofappropriate active components enabling slow release of those componentsmay also be produced by electrohydrodynamic means by providing theactive component as the core of the capsule or fibril.

[0022] Embodiments of the present invention will now be described, byway of example, with reference to the accompanying drawings, in which:

[0023]FIG. 1 shows schematically one example of a device for carryingout a method embodying the invention;

[0024]FIGS. 2a to 2 c are schematic diagrams for illustrating themechanisms by which at least partially solid or gel-like particles,fibrils and fibres, respectively, may be produced by a method embodyingthe invention;

[0025]FIG. 3 shows schematically another example of a device forcarrying out a method embodying the invention;

[0026]FIG. 4 shows schematically use of the device shown in FIG. 3 toapply a dressing to the skin surface, a wound, burn or area exposed by asurgical procedure.

[0027] FIGS. 5 to 8 illustrate various different types of nozzles oroutlets which may be used in a method embodying the invention;

[0028]FIG. 9 shows a mat or web of fibres produced using a methodembodying the present invention;

[0029]FIG. 10 shows substantially parallel fibres deposited on a surfaceusing a method embodying the present invention;

[0030]FIG. 11 shows a part cross-sectional view of another example of adevice for use in a method embodying the invention;

[0031] FIGS. 12 shows a nozzle which may be used to produce compositematerial;

[0032]FIG. 13 shows a nozzle for producing material from a mixture oftwo different liquids; and

[0033]FIG. 14 shows schematically another example of a device forcarrying out a method embodying the invention.

[0034] Referring now to the drawings, FIG. 1 shows schematicallyapparatus 1 comprising a container or reservoir 2 of liquid coupled by asupply pipe 3 to an outlet 4 via a flow regulating valve 5 ofconventional form. The valve 5 may be a manually or electricallyoperable valve. A voltage source 6 supplying a voltage of typically 15to 25 kV is coupled to the outlet 4 so as to cause liquid issuing fromthe outlet 4 to become charged. If the liquid is at least semiconducting(that is the liquid has a resistivity below about 10⁹ ohm-m), thevoltage source 5 may be coupled to the liquid upstream of the outlet 4.

[0035] In use of the apparatus, a surface area 7 such as an area of theskin of an animal, for example an area of skin of a human being, ispositioned a few centimeters, for example from 5 to 10 cm, below theoutlet 4 as shown schematically in FIG. 1. The voltage source 6 iscoupled to the outlet 4 by closing a switch (not shown in FIG. 1) andthe flow regulating valve 5 opened so that liquid is supplied undergravity to the outlet 4. The liquid is selected to be biologicallycompatible, that is not harmful or detrimental to the animal whendeposited on its skin or an open wound, and will typically have aresistivity in the range of from approximately 10² to 10⁸ ohm-meters anda viscosity in the region of from 0.1 to 1000 Poise or greater with theviscosity being dependent on whether a fibre, fibre fragments orsegments or particles are to be formed.

[0036] As described in the aforementioned GB-A-1569707 and an articleentitled “Electrodynamic Crop Spraying” by R. A. Coffee published inOutlook on Agriculture Volume 10 No. 7 1981, liquid issuing from theoutlet 4 is subject to an intense electrical field which establishes astanding wave along the surface of the liquid producing cusps or coneswhich emit jets of charged liquid.

[0037] The small perturbations which inevitably occur in the liquid jetcause the jet to become unstable and the net electrical charge in theliquid provides a repulsive force which acts against the surface tensionforces in the liquid. This would normally be expected, as described inGB-A-1569707, to cause the liquid to break up into droplets which,because both they and the outlet 4 are similarly charged, are propelledaway from the outlet 4 and each other so providing a spray or cloud ofliquid droplets. The present inventors have, however, found that byselecting the liquid and controlling the conditions of theelectrohydrodynamic process, the jet of liquid, rather than breaking upinto liquid droplets, forms a solid or gel-like fibre or forms fibrefragments (fibrils) or non-liquid droplets or particles. In use of theapparatus shown in FIG. 1, the fact that the electrohydrodynamicallyproduced material is charged and the animal body can effectively beconsidered earthed causes the material to deposit onto the surface 7 ofthe skin beneath the outlet 4. The material deposits swiftly, uniformlyand gently by the energy contained in the electric field used togenerate the material and will not overspray, nor become trapped in airstreams and swept away from the target surface. One or more layers ofsuch material may be deposited to provide a dressing to, for example,cover or protect, a wound or burn. This material being non-liquid shouldnot cause the irritation which may arise from, for example, solvents ifliquid droplets were applied to the skin.

[0038] Relative movement may be effected between the nozzle 4 and thesurface 7, in this example the surface 7 may be moved, to enablecoverage of a large area.

[0039]FIG. 2a illustrates the situation where the liquid supplied to theoutlet or nozzle 4 forms a spray of solid droplets or particles D whileFIG. 2b illustrates the situation where the liquid jet breaks up intofibrils FF and FIG. 2c illustrates the situation where the liquid jet Jforms a fibre F.

[0040]FIGS. 2a to 2 c show only one cone C and the associated jet Jemanating from a nozzle 4. The actual number of cone and jets producedwill, however, depend upon several factors, including the resistivity,permittivity and flow rate of the liquid, the dimensions of the outlet 4and the applied electric field.

[0041] In order to form the solid or gel-like droplets shown in FIG. 2a,the liquid is selected or formulated so as to become non-liquid, that isat least partially solid or gel-like, after the liquid has beenseparated by the applied electric field into liquid droplets. Where theliquid includes a solvent, this may be achieved by, for example,selecting a liquid of such a volatility and viscosity and controllingthe flow rate so that the solvent evaporates sufficiently to cause atleast partial solidification or gellification only after dropletformation. Where the liquid is a melt which is held at an elevatedtemperature during supply to the outlet, then the liquid should beselected to have a melt temperature such that the liquid solidifiesafter liquid droplet formation. This may be facilitated by quenchingusing, for example, a cold inert gas or air stream.

[0042] To form the fibrils or fibre fragments shown in FIG. 2b ₁, theliquid is selected or formulated and the flow rate controlled so thatthe Liquid jet becomes at least partially non-liquid, that is solid orgel-like, before the liquid has been separated by the applied electricfield into liquid droplets but so that the growth wave resulting fromperturbation of the jet J remains sufficiently strong to inhibitformation of a fibre and causes the jet to break up into fibre fragmentsor fibrils FF. This may be achieved by selecting the liquid and flowrate so that the liquid begins to solidify (for example by evaporationin the case of a solution or by cooling in the case of a melt) beforedroplet formation and becomes relatively brittle so that the growth wavecauses the nascent fibre to break into segments. Break up of the nascentfibre into fibrils may be facilitated by pulsing the voltage applied tothe outlet 4 so as the create an energy pulse which sets up a resonantprocess to promote breaking up of the nascent fibre. Experiments haveshown that the length of the fibrils is related to the pulse duration orfrequency with, under ideal conditions, the fibril length being equal tothe jet velocity divided by the pulse frequency so that, for example, ifthe jet velocity is 5 ms⁻¹ and a pulse frequency is 100 kHz is used, thefibrils should have a length of 50 μm. Fibrils having lengths in theregion of, for example, tens of micrometers to a few centimeters may beproduced, depending upon the particular liquid and electrohydrodynamicprocess conditions used.

[0043] In order to form the solid or gel-like fibre F shown in FIG. 2c,the liquid is selected so as to become non-liquid, that is at leastpartially solid or gel-like, after issuing from the outlet, and thegrowth wave resulting from perturbation of the jet is attenuated so thatthe jet does not break up but forms a continuous fibre which has alength determined by the time for which the electrohydrodynamic processis continued, that is the time for which the voltage is applied.Attenuation of the growth wave may be achieved by the incipientsolidification and/or by the nature of the liquid. Fibre production maybe achieved by, for example, selecting a liquid which is highly volatileor has a highly volatile component so that solidification by evaporationoccurs very quickly before droplet formation. For example fibres may beformed using a liquid comprising a polymer which on solidificationtends, because of its viscosity and/or polymer chain morphology, toresist growth wave development. Fibres may be formed using a relativelyhigh molecular weight polymer, for example a polymer having a molecularweight in the region of 140000 or more. Where the liquid used is a meltthen choosing a liquid which solidifies to a relativity plastic stateshould promote fibre formation.

[0044] The apparatus 1 shown in FIG. 1 uses a gravity feed to supplyliquids to the outlet 4 which has the advantage of simplicity. It ismost suitable for use in situations where the area of skin to which thedressing is to be applied can easily be moved beneath the outlet 4 orfor use when the liquid to be supplied may be detrimentally affected bypumping.

[0045]FIG. 3 illustrates a part cross-sectional view of another form ofapparatus 1 a suitable for use in a method embodying the invention. Theapparatus shown in FIG. 3 is, as illustrated schematically in FIG. 4,intended to be portable, in particular so as to be held in the hand 8 ofa user.

[0046] The apparatus 1 a shown in FIG. 3 comprises a housing 9 withinwhich is mounted a reservoir 2 a of the liquid to be dispensed. Thereservoir 2 a may be formed as a collapsible bag so as to avoid any aircontact with the liquid being dispensed. The reservoir 2 a is coupledvia a supply pipe 3 a to a pump chamber 10 which is itself coupled viathe supply pipe 3 and the flow regulating valve 5 to the outlet 4 in asimilar manner to that shown in FIG. 1. The voltage source 6 in thisexample is coupled to a user-operable switch SW1 which may be aconventional push button or toggle switch, for example. The voltagesource 6 may comprise, for example a piezoelectric high voltage sourceof the type described in WO94/12285 or a battery operatedelectromagnetic high voltage multiplier such as that manufactured byBrandenburg, ASTEC Europe of Stourbridge West Midlands, UK or StartSpellman of Pulborough, West Sussex, UK and typically provides a voltagein the range of from 10 to 25 kV. Although not shown, a voltage controlcircuit comprising one or more resistor capacitor networks may beprovided to ramp the voltage up smoothly. The reservoir 2 a may becoupled to the pump chamber 10 by way of a valve 11 which may be asimple non-return or one way valve or may be an electrically ormechanically operable valve of any suitable type, for example a solenoidor piezoelectric valve, operable by a voltage supplied by theaforementioned control circuit.

[0047] The pump chamber 10 may comprise any suitable form of pump, whichprovides a continuous substantially constant flow rate, for example anelectrically operable pump such as a piezoelectric, or diaphragm pump oran electrohydrodynamic pump as described in EP-A-0029301 or EP-A-0102713or an electroosmotic pump as described in WO94/12285 or amechanically-operable pump such as syringe pump operated or primed by aspring biassing arrangement operable by a user.

[0048] In use of the apparatus 1 a shown in FIGS. 3 and 4, the userfirst positions the apparatus over the area 7 to which the material isto be applied, then actuates the switch SW1 and the pump of the pumpchamber 10 to cause, when the valves 5 and 11 are opened, a stream ofliquid to be supplied to the outlet 4 whence the liquid is subjected tothe applied electric field as described above with reference to FIGS. 2ato 2 c, forming charged matter which deposits onto the said surface 7which may be the skin or on or within a wound. The user may move theapparatus or device 1 a relative to the area 7 to cover a large area.One or more layers may be formed in a manner similar to that describedwith reference to FIG. 1. The apparatus shown in FIGS. 3 and 4 has,however, the advantage that it is portable so allowing it to be usedfor, for example, first aid at the site of an accident and/or onrelatively inaccessible areas of the body and does not rely on gravityfeed.

[0049] Various different forms of outlet or nozzle 4 may be used in theapparatus shown in FIGS. 1 and 3 and 4. FIGS. 5 to 8 illustrateschematically some examples. Another possibility is the fibrecomminution site or nozzle described in WO95/26234.

[0050] The nozzle 4 a shown in FIG. 5 comprises a hollow cylinder whichis conductive or semiconductive material at least adjacent its end 4′where the voltage is to be applied in use and will in use produce one ormore jets (one cusp or cone C and jet J are shown) depending upon theresistivity and flow rate of the liquid and the voltage applied to theoutlet 4.

[0051] The nozzle 4 b shown in FIG. 6 comprises two coaxial cylinders 40and 41 at least one of which is conductive or semiconductive at leastadjacent its end 40′ or 41′ where the voltage is applied and will in useproduce a number of jets depending upon the resistivity and flow rate ofthe liquid and the applied voltage.

[0052] The nozzle 4 c shown in FIG. 7 comprises a number of parallelcapillary outlets 42 which are conductive or semiconductive at leastadjacent their ends 42′ where the voltage is applied. Each capillaryoutlet 42 will normally produce a single jet. The multiple nozzles shownin FIG. 7 have the advantage that blockage of one nozzle by relativelyviscous liquid does not significantly affect the operation of the deviceand also allow different liquids to be supplied from respectivereservoirs to different ones of the nozzles.

[0053] The nozzle 4 d shown in FIG. 8 comprises a slot-shaped nozzledefined between two parallel plates 43 which are conductive orsemiconductive at least adjacent their ends 43′ where the voltage isapplied. The use of a slot nozzle when relatively highly viscous liquidsare being used is advantageous because complete blockage of the nozzleis unlikely, as compared to the case where a relatively fine capillarynozzle is used, and a partial blockage should not significantly affectthe functioning of the device because the liquid should be able to flowround any such partial blockage. The use of a slot-shaped nozzle outletas shown in FIG. 8 also allows a linear array of jets and thus offibres, fibrils or particles or non-liquid droplets to be formed.

[0054] Where, as discussed above, the liquid being used is sufficientlyconductive to enable the voltage to be applied to the liquid rather thanthe nozzle then the nozzle may be formed of any suitable electricallyinsulative material which does not retain electrical charge for anysignificant length of time, for example glass or a semi-insulatingplastic such as polyacetyl.

[0055] The nozzle shown in FIG. 7 is designed to produce a single jetper individual outlet 42. The nozzles shown in FIGS. 6 and 8 will in useproduce a number of jets which extend generally along the electric fieldlines, with the number of jets depending upon, of course, the length ofthe slot (FIG. 8) or the diameter of the annulus (FIG. 6) and also uponthe resistivity of the liquid, the flow rate and the applied voltage.

[0056] In the case of the cylindrical nozzle shown in FIG. 5, when theflow rate is high only one jet will be produced as shown. However, atlow flow rates, the liquid tends to emerge from the outlet as a filmwhich clings to the rim of the cylinder and there forms multiple jets ina manner analogous to the annular nozzle shown in FIG. 6.

[0057] Where the resistivity of the liquid is high, for example about10⁹ ohm-m, some 10 or 20 jets, dependent upon the applied voltage andflow rate, may be formed per cm length of the nozzle, allowing the samenumber of fibres, for example, to be produced (spun). The appliedvoltage also affects the diameter of the resulting material. Thus, about10 to 15 fibres of about 10 to 20 micrometers in diameter may be formedper cm length of the slot shown in FIG. 8 from a liquid having aresistivity of about 10⁹ ohm-m when the applied voltage is 15 kilovoltsand a larger number, about 20, of fibres of smaller diameter may beformed per cm length of the slot when the applied voltage is 25kilovolts. At liquid resistivities of, for example, 10⁷ ohm-m, some 5 to10 fibres may be spun per cm length of the slot, dependent again on theapplied voltage and flow rate, with again a larger number of thinnerfibres being formed at higher voltages. The number of jets produceddecreases but their diameter increases with increasing flow rate. Byselecting the resistivity and viscosity of the liquid, the flow rate andthe applied voltage, material, for example fibres or fibrils, withdiameters from a few, about 10 nanometers (nm) to above 100 micrometers,typically 10² to 10⁴ nm, may be produced. Similar results may beachieved using the hollow cylinder nozzle of FIG. 5 or the annularnozzle of FIG. 6.

[0058] The use of a liquid which is controlled to produce fibres isparticularly advantageous for producing a wound or burn dressingbecause, as will be described below, deposition of the fibres onto thearea being covered results in a network of crossing or interlinkingfibres providing effectively an integral web or mat which has a highspecific surface area and is thus highly absorbent to fluids, whilstbeing exceptionally light. Like a conventional dressing it enables goodcoverage over an area of skin so as, for example, to protect a woundbut, unlike many conventional dressings, still enables, by virtue of thegaps between the network of fibres, air to pass through the dressing tothe wound and pus and other detritus to pass from the wound, whilepreventing ingress of bacterial matter into the wound.

[0059] By controlling the diameters of the fibres in the mannerdescribed above and/or by controlling the number of layers of fibres,dressings having a range of thickness, fluid permeability and mechanicalstrength can be formed enabling the dressing to be adapted for use ondifferent types of wounds and burns including wounds arising from severetrauma such as say motor vehicle accidents, battle wounds etc, andchronic wounds including lesions such as ulcerated veins as well as,where appropriate, surgically exposed tissue. The permeability of thedressing has been found to be a function of the diameters and spacing ofthe fibres and the motion of the nozzle over the deposition area duringapplication.

[0060] Liquids which form short fibrils or solid droplets will notgenerally form a cohesive mat or web of fibres. However, liquids whichform fibrils or solid droplets may be used in combination withconventional dressings or with dressings formed by fibres as discussedabove, for example fibrils or solid droplets produced using a methodembodying the invention may be deposited into or on a wound and thencovered with one or more layers of fibres produced by method embodyingthe invention or by a conventional dressing.

[0061] Fibres, fibrils or droplets produced by a method embodying theinvention may be deposited onto a substrate, such as a dressing, forlater application to the skin, a wound, burn or the like.

[0062] Experiments have been carried out with a number of differentpolymers and solvents. It has been found that long chain heavy molecularstructures facilitate fibre production while short chain lengthmolecular structures tend to form fragments or solid droplets. Solventswhich evaporate quickly during the jet flow may be used to facilitateformation of fibres. Suitable solvents may be, for example, methanol,propanol and water, methylene chloride, acetone and chloroform,depending upon the particular polymer used.

[0063] Experiments have been carried out in which the apparatus shown inFIG. 1 was used with water and hydrocarbon based solutions supplied to aslot-like nozzle of the type shown in FIG. 8 having a slot width ofabout 150 micrometers and a slot length of 2 cm. Liquid flow rates offrom 1 to 10 microliters per second and voltages of from 10 kV to 15 kVwere found to produce about 5 to 15 charged fibres per cm length of theslot with the fibres having diameters in the range of from 1 to 100micrometers.

[0064] Fibres have been successfully spun with polyhydroxybutyric acid,a bioresorbable polymer, and polyvinyl alcohol (PVA), a polymer solublein water and alcohols such as methanol or propanol, and pharmaceuticalpreparations for wound care, such as “New Skin” (trade mark) marketed bySmithKline Beecham which comprises nitrocellulose in an organic solution(in particular it comprises ethyl acetate, isopropyl alcohol, amylacetate, isobutyl alcohol, denatured alcohol, camphor andnitrocellulose). “New Skin” is normally applied to scratches and lightwounds with a rod or paddle because it is too viscous to be applicableby conventional spray devices. “New Skin” has however been successfullysprayed by a method embodying the invention to form fibres ofapproximately 0.5 to 5 micrometers diameter which deposited uniformlyonto skin, resulting in a firm skin-like web-film. In one specificexample neat (that is undiluted) “New Skin” was supplied at a flow rateof 4 milliliters per hour to a capillary nozzle of the type shown inFIG. 5 in the form of a 1.1 mm diameter thin-walled metal, generallystainless steel, tube. A voltage of 8.2 kV was applied to the nozzlewhich was located approximately 50 mm above an earthed depositionsurface. Multiple fibres were formed and substantially uniformlydeposited on the surface. Fibres have also been produced using undiluted“New Skin” (trade mark) with flow rates of from 1 milliliters per hourto 100 milliliters per hour.

[0065] Polyvinyl alcohol (PVA) has also been deposited in a similarmanner to the “New Skin”, using combinations of alcohol and water assolvent. Neat, undiluted PVA having a molecular weight of typically15000 has been found to tend to form solid droplets whenelectrohydrodynamically processed while PVA having a molecular weight ofabout 140000 or more tends to form fibres. Low molecular weight PVA in avolatile solvent such as ethanol tends to break up into fibrils ratherthan continuous fibres. Thus, PVA having a molecular weight in theregion of about 90000 to 140000 will tend to form fibrils and PVAfibrils having diameters of a few hundred nanometers and lengths of 0.5to 10 mm have been produced.

[0066] In another experiment, an annular nozzle of the type shown inFIG. 6 was used to which a voltage of from 5 kV to 15 kV was applied. A90% by volume solution of poly β-hydroxybutric acid (which is abioresorbable polymer) in methylene chloride was supplied at a flow rateof from 5 micro liters per second to 50 micro liters per second to thenozzle which was located at a distance of about 5 cm from human skin. Acovering layer of fibres was formed on the skin with the fibres havingdiameters, dependent on the applied voltage and flow rate, in the rangeof from about 10 micrometers to about 50 micrometers.

[0067] In another example, the apparatus shown in FIG. 1 was used with athin-walled, generally stainless steel, capillary nozzle of the typeshown in FIG. 5 having a 1.1 mm external diameter. The reservoir wasfilled with polylactic acid having a molecular weight of 144000dissolved 10% by mass in acetone and the flow regulator was controlledto provide a flow rate of 10 milliliters per hour. A voltage of 12 kVwas applied to the nozzle which was located 8 cm away from andperpendicular to a flat earthed counter electrode provided to simulate askin surface. This experiment was also repeated using a flow rate of 6.0milliliters per hour and a nozzle voltage of 11.4 kV. The surface of theflat plate was covered by a network or mass of randomly distributedfibres having diameters typically in the region of from 2 micrometers to7 micrometers.

[0068] The fibres deposit readily onto capacitive or earthed surfaceswithout any of the normal problems of applying very low mass highspecific surface materials and the electrical field ensures that thefibres deposit swiftly, gently and substantially uniformly.

[0069]FIG. 9 shows a copy of an image produced by scanning electronmicroscope of a typical mat or web of fibres 12 on a plate 13. Thefibres have, typically, a diameter of approximately 5 μm. The fibresshown in FIG. 9 are relatively randomly distributed because theirrelatively low mass, and thus low inertia, and high charge to mass ratiomeans that their movement and thus location of deposition on the surfaceis strongly influenced by the fact that they are all similarly chargedfibres. This also results in the fibres crossing one another andpossibly even blending together which should increase the overallmechanical integrity of the web or mat.

[0070] By increasing the mass of the fibres and thus their inertia, andreducing their charge to mass ratio, greater control can be achievedover the deposition of the fibres so that the location at which thefibres are deposited on the skin or wound can be controlled mainly bymoving the nozzle relative to the skin or wound and by controlling thenumber of passes and pattern of movement of the nozzle over the surface.FIG. 10 shows an example of fibres 15 of about 50 to 100 micrometers indiameter deposited onto a substrate using a slot-shaped nozzle of thetype shown in FIG. 8. As can be seen from FIG. 10, a single pass of thenozzle produces a set of approximately parallel tracks and, with two ormore passes, a relatively dense material akin to a textile can beproduced. Although the actual pattern shown in FIG. 10 was produced bydepositing fibres of a heavy build viscous paint onto paper, it will beappreciated that similar results can be achieved using other materialsuch as inert polymers of similar mass. The movement of the nozzle maybe controlled to produce any desired pattern and that for example awoven texture could be simulated. Such fibres may be used, for exampleto form a bandage.

[0071] In the examples described above, the fibres, fibrils or dropletsproduced using the method embodying the invention consist simply of aninert polymer which may be a bioresorbable polymer such aspolyhydroxybutyric acid, polyvinyl alcohol, polyglycolic acid orpolylactic acid. Biologically active ingredients may, however, be addedto the liquid before it is supplied to the outlet nozzle 4. In suchcases, the liquid may comprise a solution, suspension, microsuspension,emulsion, microemulsion, gel or even a melt containing the activecomponent or components. Possible active components are one or more ofthe following, namely pharmaceutical compounds such as analgesics,antiseptics, antibiotics, bactericides, antifungals, antiparasitics,anti-inflammatory agents, vasodilators (such as minoxidil which isbelieved to promote wound epithelialization and neovascularization),agents such as proteolytic enzymes for debridement and tissue repairpromoting materials such as for example cytokines for stimulatingcytokinetic activity to promote essential cell activities, for exampleto stimulate dendritic growth, growth factors such as fibroblast growthfactor (FGF), epithelial growth factor (EGF), transforming growth factor(TGF) that are believed to reduce scarring and others that may be usedto promote or otherwise control the sequence of events essential tonatural tissue repair, cells, peptides, polypeptides, insulin, immunesuppressants or stimulants and vaccines. Another possible activecomponents are DNA or other genetic matter for gene therapy, surfacebinding or surface recognising agents such as surface protein A, andsurfactants.

[0072] Where more than one layer of fibres, fibrils and/or particles isdeposited, then different active ingredients may be provided in thedifferent layers and different biologically active ingredients may beincluded in different fibres, fibrils or particles where a nozzle of thetype shown in FIG. 7 is used. Also biologically active ingredients maybe provided between layers, for example skin cells may be interspersedin or between layers.

[0073] The active ingredient may comprise an adjuvant that is apharmacological agent added to a drug to increase or aid its effect oran immunological agent that increases the antigenic response.

[0074] Where the resulting material is in a form of fibrils, the fibrilsmay actually stick into the surface, for example skin or soft tissue,onto which they are deposited so enabling, for example, the supply ofdrugs and other biologically active agents beneath the skin or into thesoft tissue, and may for example be used to carry DNA to cells.

[0075]FIG. 11 illustrates a modified form of the device shown in FIG. 3.The device 1 b shown in FIG. 11 is essentially similar to that shown inFIG. 3 but comprises two reservoirs 20 a and 20 b each coupled byrespective supply pipes 30 a and 30 b and possibly by non-return valves11 a and 11 b to a respective pump chamber 100 a and 100 b coupled via arespective valve 50 a and 50 b to a respective liquid supply pipe 30which terminates in a respective outlet 44 and 45 arranged so that theoutlet 45 is coaxial with and extends around the outlet 44. FIG. 12shows the outlets 44 and 45 on an enlarged scale. The device 1 b shownin FIG. 11 allows different forms of liquid to be supplied to theelectrohydrodynamic processing site provided by the outlets 44 and 45.

[0076] The reservoir 20 a coupled to the inner outlet 44 may contain asupply of a biologically active ingredient such as a pharmaceutical or asolution of DNA for example, while the reservoir 20 b coupled to theouter nozzle 45 may contain a supply of a polymer solution of the typediscussed above, for example polyhydroxybutyric acid dissolved inmethylene chloride. The device shown in FIG. 11 is operated in a similarmanner to the device shown in FIG. 3. Thus, the switch SW1 is firstactivated to supply the required voltages, typically 10 to 25 kV, theflow regulating valves 50 a and 50 b are then opened to provide therequired flow from each of the nozzles 44 and 45 and the pumps 100 a and100 b and valves 11 a and 11 b, if present, activated to supply liquidto the respective nozzles 44 and 45. The outlets of the two coaxialnozzles are designed to promote laminar flow so that the polymercontaining solution issues from the nozzle 45 so as to surround theother liquid.

[0077] By appropriate selection the molecular weight of the polymerand/or the volatility of the polymer solution, the liquids issuing fromthe combined nozzle can be caused to form a fibre or fibrils in whichthe biologically active ingredient forms a cylindrical centre core ofthe fibre or fibril or micro capsules in which the biologically activeingredient is completely encapsulated within the polymer and may stillbe in a liquid form.

[0078] For microcapsule formation it has been found preferable to reducethe percentage polymer in solution and to use a much reduced molecularweight polymer. For example a resin such as neoprene chlorinated rubberdissolved at more than about 10% by weight in trichloroethane will tendto spray fibres. However by decreasing the percentage polymer and/orusing a less volatile solvent such as, for example, propylene glycolether, microcapsules may be formed. Microcapsules have been producedusing PVA of low molecular weight, for example a molecular weight ofabout 15000, dissolved to a dilution of between about 2.5 percent and 5percent by volume in water or alcohol with a flow rate of about 1.0microliters per second. Production of microcapsules may be enhanced byusing two reactive monomers one of which is placed in each of the twoliquids to react during comminution.

[0079] The composite products produced using the device shown in FIGS.11 and 12 may be used to form a dressing in the manner described abovewhere the composite product is in the form of fibres or long fibrilsallowing for controlled release of the active ingredient as thebioresorbable polymer degrades. Where the composite products producedare fibres, fibrils or microcapsules, then these may be applied to thesurface of the skin or into a wound in combination with, for example, aconventional dressing or a dressing produced from comminuted fibres.Material from the core of a fibre or fibril may be released from theends of the fibre or fibril. Material from the core of a fibre, fibrilor microcapsule may be released through the coating if the coating ispermeable to the material contained within it or may be released as aresult of the outer coating being breached, for example by chemical orenzymic attack which causes the outer coating to dissolve or degrade, bybioresorption or biodegradation of the coating, or as a result oftemperature changes or application of pressure which causes the outercoating to rupture.

[0080] Composite products made up of three or more different layers ofmaterial may be formed by increasing the number of coaxial nozzles.

[0081] The outlet nozzle of the device shown in FIG. 11 may comprise anumber of sets of coaxial outlet nozzles 44 and 45 in a manner similarto that shown in FIG. 7 for single outlet nozzles. This would allowdifferent active ingredients to be supplied to different ones of theinner nozzles 44. The different active ingredients can thus be keptapart until actual use which is of particular advantage where the activeingredients react to form a product which itself has a low shelf life.

[0082] It will, of course, be appreciated that the apparatus shown inFIG. 1 could be modified in a manner similar to that shown in FIG. 11for FIG. 3 to produce a device capable of forming cored fibres, fibrilsor microcapsules.

[0083] As discussed above, the nozzle shown in FIG. 12 is deliberatelydesigned to avoid mixing between the two liquids which are generallyselected so as to be immiscible thereby enabling production of a coredfibre, fibril or microcapsule.

[0084]FIG. 13 shows an alternative form of nozzle which may be used inthe apparatus shown in FIG. 11. The nozzle shown in FIG. 13 is aslot-nozzle similar to that shown in FIG. 8 but provided with twoseparate channels 46 and 47 coupled to respective ones of the liquidsupply pipes so that each channel receives a different liquid. Theoutlets of the channels 46 and 47 are designed so as to createturbulence and therefore mixing of two liquids at the outlet. Thisarrangement may be used where, for example, it is desired to have somecontrol over the amount of active ingredient which may be incorporatedinto a liquid or to combine two liquids which then react. A polyurethanefoam has been formed by reacting a solution of urethane supplied via oneof the nozzles with a blowing agent supplied by the other nozzle tospray a flexible foam deposit into a wound to form a cavity wounddressing. This arrangement has the advantage that the dressing willconform to the contours of a cavity wound and may be applied withclerical cleanliness without handling. Again, an active ingredient suchas a pharmaceutically active ingredient may be incorporated into one ofthe two liquids or mixed with the two liquids.

[0085] The nozzle shown in FIG. 13 may also be used to, for example,bring reactive liquids together at the nozzle to deposit reacting orreactive product onto the skin or into a wound which should be ofadvantage where the reactive product has a very short lifetime andcannot be stored. For example, the nozzle shown in FIG. 13 has been usedexperimentally to produce a fibrin mat by supplying the enzyme thrombinto one channel and fibrinogen to the other channel.

[0086] As another possibility the device shown in FIG. 11 may bemodified to provide two separate spaced nozzles and the voltage sourcearranged to charge the two nozzles to voltages of opposite polarity in amanner similar to that described in WO94/12285 so as to enable liquiddroplets charged to one polarity to rapidly coalesce with dropletscharged to the other polarity to form ultra-small particles of fromsub-micron to a few tens of microns in diameter. Again, for example,ultra small droplets containing, for example the enzyme thrombin may besprayed at one polarity so as to rapidly coalesce with droplets of theopposite polarity containing fibrinogen to deposit a fast reactingfibrin mat to cause blood clotting, for wound sealing or for adhesion.

[0087] A method embodying the invention may also be used to producematerial capable of transfecting resident cells in situ with geneticmaterial in order to regulate cell responses. For example, a methodembodying the invention may be used to produce microcapsules comprisingDNA encapsulated in a microcapsules or complexed with an appropriatelipid material for transfecting cells. Phospholipid microcapsulesencapsulating DNA may be produced by a method embodying the invention.Other biological material such as proteins may be similarly encapsulatedor complexed with an appropriate lipid material. Proteins may also beincorporated in the lipid layer. Surface binding or surface recognisingagents such as surface protein A may be incorporated into microcapsules,especially phospholipid microcapsules, for selecting targets such ascancer cells, epithelial cells etc. Also, surfactants such as soyalecithin available from Sigma Pharmaceuticals may be incorporated in theouter surface of fibres, microcapsules or fibrils.

[0088] Fibres, fibrils or droplets or capsules produced by a methodembodying the invention may be coated with substances such assurfactants such as soya lecithin or with, for example, DNA which isrelatively sticky. This may be achieved by, for example, supplying thepolymer containing liquid to the inner nozzle in FIG. 11 and supplyingthe coating material to the outer nozzle in FIG. 11. Alternatively, aseparate spraying device, which may be a conventional orelectrohydrodynamic spraying device, may be provided so as to direct,for example, an oppositely charged spray or cloud of the coatingmaterial into the path of the material produced by the apparatus shownin FIG. 1, 2 or 11, for example.

[0089]FIG. 14 illustrates schematically a modified form of the deviceshown in FIG. 11 which may be suitable for producing fibrils ormicrocapsules for inhalation. The device shown in FIG. 14 differs fromthat shown in FIG. 11 merely by the provision of air vents 62 andelectrical discharge 60 means for discharging the fibrils ormicrocapsules and an outlet 50 adapted to receive a tube for insertioninto the mouth or trachea of a user or to receive a mask to cover themouth and nose of a user where both oral and nasal inhalation arerequired. The electrical discharging means may comprise, for example, anearthed discharge electrode 61 so as to produce gaseous ions of theopposite polarity to the charged fibrils or microcapsules so that thefibrils or microcapsules are discharged for inhalation by a user. Thedischarging means may be brought into operation by the active inhalationby the user as described in, for example, WO94/14543. The provision ofthe electrical discharge means enables the fibrils or microcapsules tobe delivered to the upper or lower regions of the lungs rather thansimply to the nasal passages. The actual location to which the fibrilsor microcapsules are delivered can be controlled by controlling anyresidual electrical charge and the precise dimensions of the fibrils ormicrocapsules may be controlled by controlling the volatility, flow rateand voltage applied to the nozzle.

[0090] The material for oral delivery may comprise liposome encapsulatedor complexed DNA for transfecting cells or may, for example comprisebiologically active ingredients such as peptides, polypeptides and otherlarge biomolecules such as insulin or growth factor, and activepharmaceutical components for enabling delivery of the active componentinto the blood stream via the lung. This should provide a quicker routeto the bloodstream than that provided by normal oral ingestion andavoids the need for injection of components which cannot be taken orallybecause of the gastric enzymes and acids present in the digestivesystem.

[0091] Where a method embodying the invention is used to produce fibres,fibrils or microcapsules comprising a core of an active ingredient, thechoice of coating material, the permeability and/or thickness of thecoating may be adjusted to adjust the timing of release of the activeingredient. For example where the coating comprises a bioresorbable orbiodegradable polymer, the half-life of the polymer may be controlled bycontrolling the permeability and/or thickness of the polymer coating by,for a specific formulation, controlling the flow rate and voltage.

[0092] A method embodying the invention may also be used to supplymaterial to body cavities other than the respiratory system. Generally,for such use, the material will be at least partially electricallydischarged before supply and means may be provided for forming an air orinert gas flow to assist the supply of the material to the body cavity.Where the body cavity is not easily accessible from the outside of thebody, then the device embodying the invention may be mounted to anendoscope or like instrument enabling the device to be inserted into thebody and to be positioned at the site where the material is required.The material may comprise any of the fibres, fibrils, particles andmicrocapsules mentioned above.

[0093] A method embodying the invention may also be used in a productionprocess to form fibrils or particles comprising a biologically activeingredient and/or fibrils or microcapsules having a core of abiologically active ingredient which may themselves be encapsulated inconventional orally ingestible capsules, enabling, especially in thecase of microcapsules, good control over the release of the activematerial.

[0094] A method and device embodying the invention may also be used fornon-medical purposes. For example, coatings of fibres, fibrils,particles or microcapsules may be formed on substrates such as paperwith good control of the thickness and uniformity of the coating. Forexample, adhesive may be deposited onto a substrate using a methodembodying the invention.

[0095] Materials formed of two or more components which have only ashort-shelf life when mixed together may be formed in a timely mannerusing a method embodying the present invention by encapsulating therespective components in respective fibres, fibrils or microcapsules sothat mixing of the various components only occurs when the componentsare released from the encapsulating material by, for example, leachingthrough the encapsulating material, rupture by pressure being applied tothe encapsulating material, temperature, or degradation, for examplebioresorption or biodegradation, of the encapsulant. Such a method maybe used to form, for example, two component adhesives which may beapplied separately or simultaneously to a surface as cored fibres,fibrils or microcapsules by a method embodying the invention.

[0096] Other materials such as perfumes, insecticides, aromas, vapours,inks, dyes, lubricants, insect repellents etc., may be encapsulated infibres, fibrils or microcapsules and deposited on a surface using amethod embodying the invention, allowing the encapsulated ingredient tobe released in a time-controlled manner as discussed in the previousparagraph, for example by application of pressure to the surface.

[0097] A method embodying the invention may also be used to produce aprotective coating which may contain an active protective ingredientsuch as an anti-corrosive or a lubricant. For example, temporaryprotective coatings of delicate articles or articles liable to corrosionmay be provided by depositing a web or mat on the surface of the articleusing a method embodying the invention.

[0098] Webs or mats formed using a method embodying the invention mayalso be sprayed or deposited over, for example, delicate crops such asgrapes or strawberries so as to protect them from environmental effectssuch as frost, sun-damage, etc. Such a web may incorporate activeingredients such as insecticides, fungicides, miticides and the like tofurther protect the crop.

[0099] Generally, the capacitive nature of materials such as skin andthe moisture content of the air should be sufficient for deposition ontoa surface to occur simply by electrostatic attraction. However, where itis desired to deposit a large amount of material, then it may benecessary to earth the surface or to maintain it at a lower or oppositepotential to the charged matter.

[0100] A method and device embodying the invention may also be used forsupplying material to cavities other than body cavities and to concavesurfaces. In such circumstances, the charged matter will generally be atleast partially electrically discharged before it reaches the cavity orconcave surface.

[0101] As used herein, the term “particle” includes solid, partiallysolid and gel-like droplets and microcapsules which incorporate solid,partially solid, gel-like or liquid matter. The term “active ingredient”means material which is compatible with and has an affect on thesubstrate or body to which it is to be applied and the term“biologically active ingredient” or “biologically active material” meansmaterial which is compatible with and has an affect (which may forexample be biological, chemical or biochemical) on the animal or plantto which it is to be applied and includes, for example, medicaments suchas proprietary medicines, pharmaceutical medicines and veterinarymedicines, vaccines, genetic material such as DNA, cells and the like.

1. A method for forming at least partially solid material, whichcomprises subjecting liquid at an outlet to an electric field therebycausing the liquid to form at least one jet of electrically chargedliquid, the liquid being such that after formation the at least one jetforms a fibre or breaks up into fibre fragments or particles.
 2. Amethod of forming a coating or covering on a surface, which comprisessubjecting liquid at an outlet to an electric field in the vicinity ofthe surface thereby causing the liquid to form at least one jet ofelectrically charged liquid, the liquid being such that after formationthe at least one jet forms a charged fibre which is attracted to saidsurface and deposits onto said surface or breaks up into charged fibrefragments or charged particles which are attracted to and deposit ontosaid surface.
 3. A method of forming a dressing for an area of an animalsuch as a wound, a burn or an area exposed by a surgical procedure,which comprises subjecting liquid to an electric field at an outlet inthe vicinity of the area to be dressed thereby causing the liquid toform at least one jet of electrically charged liquid, the liquid beingsuch that after formation the at least one jet forms a charged fibrewhich is attracted to said area and deposits onto said area, or breaksup into charged fibre fragments which are attracted to and deposit ontosaid area, so as to form a mat or web on said area to be dressed.
 4. Amethod of forming a dressing for a wound, a burn or an area exposed by asurgical procedure, which comprises subjecting liquid to an electricfield at an outlet adjacent a substrate to be applied to the wound, burnor area exposed by a surgical procedure, thereby causing the liquid toform at least one jet of electrically charged liquid, the liquid beingsuch that after formation the at least one jet forms a charged fibrewhich is attracted to said substrate and deposits onto said substrate orbreaks up into charged fibre fragments or particles which are attractedto and deposit onto said substrate so as to form a layer on saidsubstrate.
 5. A method of depositing material into a cavity or onto aconcave surface, which comprises subjecting liquid to an electric field,thereby causing the liquid to form at least one jet of electricallycharged liquid, the liquid being such that after formation the at leastone jet forms charged matter comprising a charged fibre, charged fibrefragments or charged particles and at least partially electricallydischarging the charged matter prior to supply to the cavity or onto theconcave surface.
 6. A method according to claim 5 , which furthercomprises supplying the at least partially electrically dischargedmatter to the said cavity or concave surface from a location remote fromsaid cavity or concave surface.
 7. A method according to any one ofclaims 2 to 6 , which comprises repeating or continuing the depositionprocess to deposit a number of layers one on top of the other.
 8. Amethod according to any one of claims 2 to 7 , which further comprisesdepositing a different type of material onto said surface or area.
 9. Amethod according to claim 8 , which comprises depositing the differentmaterial by electrohydrodynamically processing a different liquid toform material comprising at least one of a fibre, fibre fragments andparticles.
 10. A method according to any one of claims 2 to 9 , whichcomprises effecting relative movement between the at least one jet andthe surface or area during deposition.
 11. A method according to any oneof the preceding claims, which further comprises subjecting a furtherliquid to the electric field, the two liquids being such that afterformation the at least one jet forms a fibre which has a core formedsubstantially by one of the two liquids and a coating formedsubstantially by the other of the two liquids or breaks up into fibrefragments or particles which have a core formed substantially by one ofthe liquids and a coating formed substantially by the other of the twoliquids.
 12. A method of forming composite matter, which comprisessupplying a liquid to a first outlet and supplying a further liquid to asecond outlet located adjacent the first outlet and subjecting theliquids to an electric field so as to form at least one jet, the liquidsbeing such that, after formation, the jet forms a fibre which has a coreformed substantially by one of the two liquids and a coating formedsubstantially by the other of the two liquids or breaks up into fibrefragments or particles which have a core formed substantially by one ofthe liquids and a coating formed substantially by the other of the twoliquids.
 13. A method for producing material for supply to therespiratory system of an animal, which method comprises supplying liquidto a comminution site; generating an electric field at the comminutionsite to cause the liquid to form at least one jet of liquid, the liquidbeing such that after formation the at least one jet breaks up intoelectrically charged comminuted matter comprising fibre fragments orelectrically charged at least partially solid particles; and at leastpartially electrically discharging the comminuted matter prior to supplyto the respiratory system of the animal.
 14. A method according to claim13 , which further comprises subjecting a further liquid to the electricfield at the comminution site, the two liquids being such that afterformation the at least one jet breaks up into fibre fragments orparticles which have a core formed substantially by one of the liquidsand a coating formed substantially by the other of the two liquids. 15.A method according to any one of the preceding claims, wherein the or atleast one of the liquids comprises a biologically active ingredient. 16.A method according to any one of claims 1 to 12 , wherein the liquid orat least one of the liquids comprises one or more biologically activeingredients selected from the group consisting of a proteolytic enzyme,a cytokine, a growth factor such as one of fibroblast growth factor,epithelial growth factor and transforming growth factor, collagen,fibrinogen, an antibiotic, an antiseptic, an antifungal, an analgesic,an antiparasitic, a batericide, DNA or other genetic matter, cells, apeptide or polypeptide, insulin, an adjuvant, an immune suppressant orstimulant, a surface binding or surface recognising agent such assurface protein A, a surfactant, and a vaccine.
 17. A method accordingto claim 13 or 14 , wherein the or at least one of the liquids comprisesone or more biologically active ingredients selected from the groupconsisting of DNA, a peptide or polypeptide, insulin, and growth factor.18. A method according to any one of the preceding claims, wherein theor one of the liquids comprises a polymer or resin.
 19. A methodaccording to any one of the preceding claims, wherein the or one of theliquids comprises a bioresorbable or biodegradable material.
 20. Amethod according to any one of the preceding claims, wherein the or oneof the liquids comprises animal collagen or fibrinogen.
 21. A methodaccording to any one of claims 1 to 17 , wherein the or at least one ofthe liquids comprises polyvinyl alcohol, polyhydroxybutyric acid,polyglycolic acid, polylactic acid, nitrocellulose or a polysaccharide.22. A method according to any one of the preceding claims, whichcomprises coating a fibre, fibril or particle with another material. 23.A method according to claim 22 , which comprises coating a fibre, fibrilor particle with a biologically active material such as DNA, asurfactant, a surface recognition protein or a lipid.
 24. A methodaccording to any one of claims 1 to 5 , wherein the liquid is selectedto form fibre fragments or particles comprising a biologically activematerial such as DNA coated or complexed with a liposome.
 25. A methodof forming a composite material, which comprises supplying first andsecond liquids separately to a site where the liquids mix and subjectingthe liquids to an electric field to form at least one liquid jet, thefirst and second liquids being selected to mix together so as to form asingle body of material.
 26. A method according to claim 25 , whereinone of the liquid comprises thrombin and the other of the liquidscomprises fibrinogen which react together to form a fibrin mat.
 27. Amethod according to claim 25 for forming a composite for covering acavity wound, wherein one of the liquids comprises urethane and theother a blowing agent which react together to form a flexiblepolyurethane foam which at least partially fills the cavity.
 28. Amethod of depositing fibres on a surface, which comprises supplyingliquid comprising polylactic acid having a molecular weight in theregion of 144000, dissolved 10% by mass in acetone, at approximately 10milliliters per hour to an electrohydrodynamic site located at about 5to 10 cm above the surface.
 29. A method of depositing fibres on asurface, which comprises supplying liquid comprising nitrocellulose atapproximately four milliliters per hour to an electrohydrodynamic sitelocated at about 5 to 10 cm above the surface.
 30. A device fordepositing material onto a surface, which comprises a supply of liquid,means for subjecting said liquid to an electric field at an outlet tocause the liquid to form at least one jet of electrically chargedliquid, the liquid being such that the at least one jet forms a fibre orbreaks up into fibre fragments or particles which are attracted to anddeposit on said surface when the device is placed in the vicinity ofsaid surface during use.
 31. A device for producing material for supplyto a cavity or to a concave surface, which comprises a supply of liquid,means for subjecting said liquid to an electric field at an outlet tocause the liquid to form at least one jet of electrically chargedliquid, the liquid being such that after formation the at least one jetforms charged matter comprising a charged fibre or charged fibrefragments or charged particles, and means for at least partiallyelectrically discharging the charged matter before it reaches the cavityor concave surface.
 32. A device according to claim 31 , furthercomprising means for providing an air or inert gas flow to assist supplyof the material to the cavity or concave surface.
 33. A hand holdabledevice for applying a dressing to an area of an animal such as an areaof skin, a wound, a burn or an area exposed by a surgical procedure,which device comprises a supply of liquid, means for supplying saidliquid to an outlet; and means for subjecting the liquid to an electricfield at the outlet to cause the liquid to form at least one jet ofelectrically charged liquid, the liquid being such that after formationthe at least one jet forms charged matter comprising a charged fibre orcharged fibre fragments or charged particles so that when the device ispositioned in use adjacent said surface so as to direct said jet towardssaid area said charged matter is attracted to and deposits on said areato form a dressing.
 34. A device according to any one of claims 30 to 33, which further comprises a supply of a further liquid, means forsupplying the further liquid to said outlet, the two liquids being suchthat, in use of the device, after formation the at least one jet forms afibre which has a core formed substantially by one of the two liquidsand a coating formed substantially by the other of the two liquids orbreaks up into fibre fragments or particles which have a core formedsubstantially by one of the liquids and a coating formed substantiallyby the other of the two liquids.
 35. A device according to any one ofclaims 30 to 34 , wherein the liquid or a liquid has features orcharacteristics as recited in any one of claims 15 to 21 , dependent onthe intended use of the device.
 36. A fibrin mat formed byelectrohydrodynamically processing thrombin and fibrinogen.
 37. A mat orweb comprising at least one of at least one fibre, fibrils, andparticles formed by electrohydrodynamically processing at least oneliquid.
 38. A dressing for a wound or burn comprising a mat or web inaccordance with claim 37 .
 39. A substrate carrying a coating comprisingelectrohydrodynamically formed matter comprising at least one of atleast one fibre, fibre fragments or fibrils and particles.
 40. A fibre,fibre fragment or capsule having a core of an active ingredient and aprotective coating of, for example, a polymer, formed byelectrohydrodynamic processing of at least two liquids.
 41. A method offorming at least partially solid or gel-like material, which comprisessupplying a liquid to a single outlet, subjecting liquid issuing fromthe outlet to an electric field thereby causing the liquid to form atleast one jet of electrically charged liquid, the liquid at leastpartially solidifying or gellifying after formation of the at least onejet to form a fibre or to form fibre fragments or particles.